PROJECT SUMMARY In the next phase of this longstanding project, we will conduct several cross-sectional and longitudinal studies focused on a dimensional approach to classification based on the shared features of internalizing disorders (IDs), large-scale clinical evaluation of several cognitive processing paradigms commonly used in cognitive and neuroscience studies of IDs, explication of genetic factors that influence temperament, cognitive processing biases, and the severity and course of ID psychopathology, and the refinement of the measurement of emotion dysregulation to examine the unique contribution of these constructs in predicting the severity and course of ID symptoms. 1,250 patients will be assessed with a broad suite of measures (e.g., clinical rating, self-report, laboratory tasks) of temperament, cognitive processing, vulnerability (e.g., emotion dysregulation), life stress, and ID symptoms, and will provide a blood or saliva sample for genetic analysis; 750 of these patients will be re-evaluated at 12- and 24-month follow-up (and 200 patients will be re-administered the cognitive processing tasks and study questionnaires following unified protocol treatment). These data will be used in studies that entail: (a) cross-sectional and longitudinal evaluation of a dimensional classification system based on the cross-cutting features of IDs; (b) evaluation of the differential predictive relationships of multiple aspects of cognitive processing (e.g., attention bias, emotion recognition, emotional memory) in cross-sectional and time-series structural models of temperament and ID psychopathology; (c) extensive measurement model evaluation of leading measures of emotional dysregulation and the relevance of emotional dysregulation to the phenomenology, severity, and temporal course of various ID symptom domains, (d) the strength and specificity of the effects of novel candidate genes derived from emerging GWAS on temperament, cognitive processing biases, and the severity and temporal course of ID psychopathology (and the potentiating effects of life stress and treatment), and (e) psychometrically oriented studies to address focal issues in measurement and classification. Key contributions of this work, which is focused on the cross-cutting dimensional features of IDs, include validation of a more robust organizational scheme that points us in the direction of etiology and prevention and predicts more precisely appropriate treatment selection, prognosis, and course. This work will also inform neurobiological studies by explicating a more valid and robust set of psychopathology and vulnerability constructs and mechanisms on which to base such investigations.